National and International Spread of Antimicrobial Resistance: Clones and Genes Professor Alan Johnson, Health Protection Services - HPA.

National and International Spread of Antimicrobial Resistance:

Clones and Genes

Professor Alan Johnson,

Health Protection Services - HPA

Antimicrobial Resistance

• Streptococcus pneumoniae

• Staphylococcus aureus

• Escherichia coli

Global Spread of Multi-Resistant Clone of Streptococcus pneumoniae (Spain23F-1)

Tennessee

Cleveland

Mexico

Colombia

Brazil

ArgentinaUruguay

Chile South Africa

SingaporeMalaysia

ThailandPhilippines

Hong KongTaiwan

South KoreaSpain

FranceBM42001978 ?

Finland

Munoz et al . J Infect Dis 1991; 164:302-06

Pneumococcal Molecular Epidemiology Network

Clone Serotype Resistance pattern

Spain23F-1 23F PEN, CHL, TET

Spain6B-2 6B PEN, CHL, TET

Spain9V-3 9V PEN

Tennessee23F-4 23F CTX, ERY

Spain14-5 14 PEN, CHL, TET

Hungary19A-6 19A PEN, ERY, CLIN, CHL, TET

S. Africa19A-7 19A PEN

S. Africa6B-8 6B PEN

England14-9 14 ERY

SCR14-10 14 PEN, ERY, CLIN, CHL, TET

PMEN, Pneumococcal Molecular Epidemiology Network: http://www.sph.emory.edu/PMEN/

Pneumococcal Bacteraemia in a British District General Hospital, Jan 2000-Mar 2001

• 56 cases of pneumococcal bacteraemia

• 18 isolates (32%) were antibiotic-resistant

• Three isolates of Spain9V-3 clone (pen-R)• 14 isolates of England14-9 clone (ery-R)• One isolate of Spain6B-2 clone (multi-R)

Birtles A et al. J Med Microbiol 2004; 53: 1241-1246

Pneumococcal vaccines

• Pneumococci comprise ~90 serotypes

• Polysaccharide capsule is a virulence determinant (inhibits phagocytosis)

• Capsule antigens form basis for vaccines

• 7-valent conjugate vaccine (2006)

• 13-valent conjugate vaccine

0%

5%

10%

15%

20%

25%

30%

35%

40%

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Res

ista

nce

(%

)Erythromycin Resistance in Invasive

Pneumococci, England and Wales

PCV-7

2mo to <2yrs

Older patients

Henderson K et al. J Antimicrob Chemother 2010; 65: 369-70.

Bacteraemia Due to MRSA, England & Wales

0

10

20

30

40

50

92 93 94 95 96 97 98 99 00 01 02

Year

% M

RS

A

Hospitals in England & Wales Sending EMRSA-15/16 to Reference Laboratory

Correlation of MRSA and Use of Macrolides, Cephalosporins and Fluoroquinolones

Monnet DL et al. EID 2004; 10:1432-41.

• Ciprofloxacin is excreted in sweat

• Disruption of normal skin microflora?

• Colonization of skin by ciprofloxacin-resistant MRSA?

Spread of EMRSA-15/16

Distribution of MRSA Spa Types in Europe

Epidemiology of Cephalosporin Resistance in UK is Changing…

• 1980-90s:

• Nosocomial (e.g. ICUs)• Commonly Klebsiella spp.• TEM/SHV ESBLs

• Since 2003:

• Commonly E. coli• CTX-M type ESBLs• UTIs in elderly patients in the community

(difficult to determine if community or HCAI)

PFGE Profile of CTX-M-producing E. coli

• 5 related strains

• Serotype O25:H4

• MLST 131

Woodford N et al.J Antimicrob Chemother 2004; 54: 735-43

• Other isolates diverse

Spread of E. coli Strain A

• CTX-M-15• Serotype O25:H4• Sequence type 131• Global spread

International Spread of E. coli 025:H4 ST131 with CTX-M-15

PFGE Profile of CTX-M-producing E. coli

• 5 related strains

• Serotype O25:H4

• MLST 131

Woodford N et al.J Antimicrob Chemother 2004; 54: 735-43

• Other isolates diverse

Bacterial Plasmids

Conjugating bacteria

• Vancomycin-resistant enterococci• Klebsiella pneumoniae• Acinetobacter baumanii• MDR TB• Cephalosporin-resistant gonococci• Carbapenemase-producing Gram-negative bacteria

Spread of AMR

• Antibiotic resistance involves both strain and gene spread• Why are some strains epidemic and others not?• How do we prevent strain spread (local/national/international)?• Can we prevent plasmid spread?• How important is plasmid spread in the gut?• Epidemiology of resistance in commensal bacteria?• Interventions (e.g. rapid tests; antibiotic stewardship)?

What We Do and Don’t Know